A further continuation of an established, interdisciplinary research effort, between computer scientists and experts in neuromuscular disease, is proposed. The long range goal of this entire project is to make quantitative morphometric analysis of muscle and nerve fibers more accurate, less tedious, and hence more available for research and clinical applications. The specific aims of the project are directed towards developing and validating highly automated morphometric techniques to supplement or replace the manual histomorphometric methods that are currently used in the analysis of muscle and nerve biopsies. Such automated techniques should prove to be more reliable and useful than their tedious and error-prone manual counterparts. The methodology is sophisticated, computer assisted image analysis, with a strong emphasis on "artificial intelligence". It also involves computer modeling. Our system scans, digitizes, and analyzes muscle and nerve biopsies directly from slides, with minimal human interaction. Results are monitored visually and resulting measurements and hard copy images are produced on simple dot-matrix printers. During the first three years of this project, we determined optimal preparation methods, developed the relevant basic image analysis techniques and tested them on the representative tissue samples. We also developed a novel measure of type grouping, the CDI, and developed a basic computer model of denervation/reinnervation. During the last 2.25 years we streamlined and optimized the system to perform in a cost- effective manner, both in a clinical laboratory setting, and in a research production mode. The model is being used to explore the underlying mechanisms of a variety of denervating diseases. Now we propose to, (i) continue a series of experiments, applying the techniques, to demonstrate their usefulness in actual research and clinical applications, (ii) to continue explorations with the model, to further the understanding of denervating diseases, (iii) to disseminate the knowledge and understanding of these techniques by developing a central resource for the analysis of muscle and nerve biopsies, at our laboratory, and (iv) to adapt the software system to run first on a microVAX II, then an IBM PC/AT with appropriate display/digitization hardware, in order to make the system "transportable" to other laboratories.